• Myocardial Infarction
• Diabetes Mellitus
• Diabetes & Endocrinology Clinical Trials

• Myocardial Infarction
• Endocrinology
• Diabetes & Metabolic Syndrome
• Diabetes Mellitus
• Diabetes & Endocrinology Clinical Trials

Liraglutide, an analogue for human glucagon-like peptide 1, is approved for patients with type 2 diabetes mellitus (T2DM) and is associated with HbA1C reductions of 1.0% to 1.5% and moderate weight loss. Diabetes is associated with a 2-fold increased risk of cardiovascular (CV) events. The ongoing Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results — A Long Term Evaluation trial [LEADER; NCT01179048] is evaluating the CV safety of liraglutide, in accordance with requirements of the United States Food and Drug Administration. The study design and characteristics of the enrolled patients were reviewed by Steven P. Marso, Saint Luke's Mid America Heart Institute, Kansas City, Missouri, USA.

From 2010 to 2012 at 410 sites in 32 countries, 9340 patients with T2DM and a HbA1C ≥7.0% with (≥50 years) or without (≥60 years) prior CV disease (CVD) were randomized to liraglutide (0.6 to 1.8 mg QD) or placebo, plus standard of care. The patients will be followed for at least 3.5 years and up to 5 years in the event-driven trial. The patients are treated with oral antidiabetic agents, basal or premix insulin, or both. The primary outcome is the time to the first occurrence of CV death, stroke, or nonfatal myocardial infarction (MI).

A unique aspect of LEADER, stated Dr. Marso, is the number of adjudicated endpoints in the trial, including all-cause mortality, acute coronary syndromes, cerebrovascular disease, heart failure, neuropathy, nephropathy, retinopathy, pancreatitis, cancers, and thyroid disease.

The analysis of the primary endpoint is a 2-step process. Noninferiority of liraglutide will be established if the upper 2-sided 95% CI for the relative risk of the primary endpoint is <1.3. Superiority of liraglutide compared with placebo will be assessed only if noninferiority is established, and superiority will be established if the hazard ratio of the upper range of the 2-sided 95% CI is <1.0.

The majority of the patients (81.7%) had prior CVD. The proportion with reduced renal function was 19.9% (n=1854) with an estimated glomerular filtration rate (eGFR) 30 to 59 mL/min/1.73 m², and 1.9% with an eGFR <30 mL/min/1.73 m² (n=177).

The patients had a mean age of 64.3 years, a mean body mass index of 32.5 kg/m²; 36% in the overall group were women (33.5% prior CVD; 45.4% no prior CVD groups), and about 12% were current smokers. Table 1 presents key diabetes-related clinical characteristics and Table 2 details CV risk factors at baseline.

The LEADER trial is expected to demonstrate conclusive evidence regarding the CV safety of liraglutide compared with standard of care for a global population of patients with T2DM. Results are anticipated in 2016.

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